An update on the dosimetric analysis of concurrent radiation therapy and trastuzumab on early cardiac events.

Abstract

121 Background: The impact of radiation therapy (RT) with concurrent trastuzumab on early cardiac morbidity is relatively unknown. Trastuzumab’s radiosensitizing properties may augment both early and late effects of RT. This retrospective review update provides an analysis of cardiac event (CE) development in patients treated with concurrent RT and trastuzumab with a focus on RT heart dose. Methods: Sixty-five patients treated with concurrent RT (30 left, 33 right, 2 bilateral) and trastuzumab at the University of Alabama at Birmingham were identified. Patient data for pre-existing heart disease, cardiac risk factors, drug regimen, and CEs were recorded. Dosimetric parameters of maximum heart dose, mean heart dose, heart volume receiving 5, 10, 15, 20 and 30Gy (V5, V10, V15, V20, V30) were also analyzed. Endpoints include the occurrence of CEs at any time in relation to RT and those specifically after the start of RT. Results: In addition to receiving trastuzumab, 80% of patients received doxorubicin. 15.4% had preexisting heart disease. The mean heart dose for all patients was 248cGy. With a median follow-up of 24.5 months, six patients developed CEs (9.2%), and three of these cases occurred after RT initiation (4, 4, and 0.5 months post-RT). All six CEs occurred during treatment with trastuzumab and consisted of congestive heart failure. Analysis of the heart dose maximum, mean, V5, V10, V15, and V20, V30 were similar in patients with and without CEs, and small differences between groups did not reach statistical significance. CE incidence was significantly associated with smoking (p=0.0037) but not hypertension, diabetes or pre-existing heart disease. Conclusions: This updated retrospective dosimetric analysis did not find a correlation between concurrent trastuzumab and RT on the development of early cardiac events. Modern era RT with 3D conformal planning, the use of heart blocks, and breath hold techniques will continue to decrease the dose to the heart. Longer follow-up will be needed for analysis of the impact of modern technologic advances and late cardiac morbidity.